Estrogen therapy in postmenopausal women is associated with reduced cardiovascular events, the mechanism of which is unclear. Because oxidation of low density lipoprotein may contribute to atherogenesis, we measured susceptibility of low density lipoprotein to peroxidation before and following infusion of 17 beta-estradiol 20 ng/min for 20 minutes into the brachial artery of 6 postmenopausal women. Low density lipoprotein oxidation was assessed by the formation of conjugated dienes following the addition of CuCl2 using spectrophotometric absorbance at 234 nm. We measured the lag time to onset of oxidation and the maximal oxidation rate. Following the infusion of estradiol, associated with an increase in the venous estradiol level from 2+/-4 to 595+/-184 (mean +/- standard deviation), the lag time to onset of oxidation increased significantly by almost an hour with a trend towards a decrease in the maximum oxidation rate. Thus, we conclude that estradiol acutely decreases the oxidative capacity of low density lipoprotein in postmenopausal women and may contribute to the anit-atherogenic effect of estrogen.